IGH/MYEOV Translocation, Dual Fusion LPH045 - Detail

The most common translocation in Multiple Myeloma is the t(11;14)(q13;q32) which accounts for 15-20% of cases that were identified by FISH¹. These translocations lead to overexpression of Cyclin D1 in about 25% of cases² and lead to alterations in the switch regions of the IGH gene³. Unlike Mantle Cell Lymphoma (MCL), where the breakpoints are clustered in a 1kb region 120kb centromeric of the CCND1 gene (BCL1), the breakpoints in Multiple Myeloma cases are dispersed within a 360kb region between CCND1 and MYEOV (MYEloma OVerexpressed) in band 11q13⁴. MYEOV is a putative oncogene, located 360kb away from CCND1 which is thought to be activated in the translocation by it becoming closely associated with IGH enhancers. In contrast to IGH rearrangements in other neoplasms, those found in Multiple Myeloma have IGH breakpoints predominantly in the C/J region which, in the case of MYEOV, brings the MYEOV gene under the control of the 3'Eα1 enhancer⁴. In CCND1 translocations by contrast, the Eμ enhancer controls CCND1 expression. Both of these illegitimate recombination events however, provide a poor prognosis for the patient and are thought to be independent.

Reference:/Bibliographie/Literatur/Bibliografia

1. Ohno H et al (1997) Leuk Lymphoma 27: 53-54
2. Ueda C et al (2002) Leuk Lymphoma 43: 1375-81
3. Akasaka H et al (2000) Cancer Res 60: 2335-41
4. Chang CC et al (1996) PNAS 93: 6947-52